Intravenous Administration of Serotonergic Psychedelics Produce Short-lasting Changes in Sleep-Wake Behavior and High Gamma Functional Connectivity in Rats

OpenAlex  – October 14, 2025

Source: OpenAlex

Summary

Psychedelics minimally impact sleep, yet profoundly alter brain activity. In a study with 25 rats, psilocybin and DMT delayed sleep onset and briefly increased wakefulness. These Psychedelics and Drug Studies highlight Neurotransmitter Receptor Influence on Behavior, showing psilocybin enhanced high gamma brain connectivity during wakefulness and sleep. While this research focuses on serotonin, other drug studies, like a Nicotinic Acetylcholine Receptors Study, explore diverse neural systems to understand drug effects.

Abstract

Abstract Background and Purpose Given the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental health. Here, we investigated the effects of intravenous psilocybin and DMT on sleep-wake states and EEG spectral power and functional connectivity in rats. Experimental Approach Sprague Dawley rats (n=25, 13 male) were surgically instrumented to record high-density EEG (27 electrodes) and EMG during 12-h light and 12-h dark cycle after intravenous psilocybin (2.5 mg/kg, 10 mg/kg), DMT (3.75 mg/kg, 7.5 mg/kg) or 0.9% saline. The EEG/EMG data were scored in 4-second epochs into wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. EEG spectral power and corticocortical coherence, a surrogate for functional connectivity, were computed in 12-second epochs. Key Results Psilocybin and DMT delayed the onset of SWS and REM sleep, and caused a short-lasting increase in wakefulness and decrease in SWS. Psilocybin also produced a 1) decrease in REM sleep, 2) decrease in theta power and coherence and increase in high gamma power and coherence during wake and SWS, and 3) increase in high gamma coherence during REM sleep. DMT increased gamma coherence only during wakefulness. Conclusions and Implications Serotonergic psychedelics have minimal effects on sleep-wake states. The enhanced high gamma functional connectivity suggests that the psychedelic-induced changes in EEG/neural dynamics can occur independent of the arousal states.

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